Beginning: November 2015
Supervisor: MOLMERET Maëlle
Co-supervisor: BARAQUET Claudine
Biofilms are surface-attached bacteria embedded in a self-produced matrix of polysaccharides, proteins and nucleic acids. In marine environment biofilms, and subsequent colonization by algae or other organisms (micro or macro fouling), causes economic and environmental drawbacks for marine industries such as decreasing hydrodynamic efficiency of ships or affecting equipment function.
Understanding how marine bacteria adhere and form biofilms on the surface of certain materials is crucial to develop new coatings with targeted anti-biofilm properties.
In many bacteria, biofilm formation is regulated by c-di-GMP (cyclic-di-guanosine monophosphate). C-di-GMP is an ubiquitous second messenger in bacteria, where it affects the transition between a motile planktonic lifestyle and an adhesive biofilm lifestyle. High intracellular c-di-GMP is usually associated with biofilm production. C-di-GMP is synthesized by diguanylate cyclases (DGC), degraded by phosphodiesterases (PDE). Because of the widespread conservation of c-di-GMP signaling in bacteria and their critical role in biofilm formation, inhibition of this pathway offers an attractive approach to interfere with biofilm formation. In addition, associated enzymes are not encoded in eukaryotic organisms and these processes are not essential for growth, reducing the risk of toxicity and the risk of selection for resistant organisms.
The project is based on the screening of chemically engineered and natural compound libraries, the rational optimization of the identified inhibitors, as well as the selection of anti-biofilm efficiency of combined inhibitors. The first step of this project is to construct a c-di-GMP reporter strain that can be introduced in different marine bacterial species to measure the intracellular concentration of c-di-GMP. To identify new molecules, which antagonize c-di-GMP signaling, we will perform structure-activity relationships (SAR) studies oriented toward c-di-GMP signaling as well as a broader screen of rationalized chemical libraries using the c-di-GMP reporter strain.
We hope to obtain new molecules able to decrease intracellular c-di-GMP concentration and therefore able to decrease biofilm formation. Inhibitors can target signal synthesis, signal perception, signal sequestration as well as inducing signal degradation.